Utility of preclinical assays to assess stored platelet function
Purpose of review: Increased use of platelets and the brief shelf life allowed by storage at 22 °C are promoting exploration of new methods to store platelets. As storage may affect the hemostatic efficacy of platelets, it is very important to assess their in-vivo hemostatic efficacy. The potential usefulness of preclinical models in evaluating methods for storing platelets will be discussed. Recent findings: The use of new technologies to examine the in-vitro characteristics of stored platelet products continues to evolve. Although in-vitro evaluation, coupled with posttransfusion recovery in healthy volunteers and...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

New mAb therapies in multiple myeloma: interference with blood transfusion compatibility testing
Purpose of review: Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients. Recent findings: CD38 is weakly expressed on human erythrocytes. Since the first reports on the inte...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Fresh versus old red cell transfusions: what have the recent clinical trials found?
Purpose of review: Red blood cell transfusion is a common treatment for anaemia worldwide, but concerns continue to be raised about adverse effects of cellular blood components, which are biological products. One hypothesis for the adverse effects associated with blood transfusion is the harmful effects of storage on red cells that have been demonstrated in laboratory and animal studies. Over the past few years, a number of more significant randomized controlled trials comparing ‘fresh’ versus ‘older’ blood have been published in an attempt to address the clinical consequences of storage age, with t...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Red blood cell alloimmunization: new findings at the bench and new recommendations for the bedside
Purpose of review: To summarize recent discoveries from clinical studies and animal models that contribute to understanding the alloimmune response to non-ABO blood group antigens. Recent findings: Several studies have confirmed high rates of alloimmunization among patients requiring chronic red blood cell (RBC) transfusion. Moreover, ‘triggers’ for alloantibody development in the transfusion setting have been identified, with a number of investigations linking recipient inflammation to a higher likelihood of alloimmunization. Additional associations between human leukocyte antigen expression and CD4+ T-cell m...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Whole blood: back to the future
We present data comparing whole blood with blood components and summarize the data that support increased availability of whole blood for patients with life-threatening bleeding. Recent findings: Recent data indicate that whole-blood transfusion is associated with improved or comparable survival compared with resuscitation with blood components. These data complement randomized controlled trials indicating that platelet-containing blood products stored at 4 °C have superior hemostatic function, compared with platelet-containing blood products at 22 °C. Whole blood is rarely available in civilian hospitals and,...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Haematopoietic stem cell transplantation in inborn errors of metabolism
Purpose of review: This review summarizes the main results of haematopoietic stem cell transplantation (HSCT) in selected inborn errors of metabolism (IEMs). Recent findings: Early diagnosis and immediate referral to an IEM specialist is of paramount importance to improve clinical outcome: patients who are transplanted early or in their presymptomatic phase generally achieve better correction of their somatic symptoms and neurocognitive development. Long-term outcome in children with Hurler syndrome is influenced by age at HSCT, baseline clinical status and post-HSCT enzyme levels. Myeloablative Busulfan-based conditionin...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Allogeneic stem cell transplantation for sickle cell disease
Purpose of review: As the safety and availability of allogeneic hematopoietic stem cell transplantation (HSCT) have improved, this procedure is becoming a viable option for nonmalignant conditions such as sickle cell disease (SCD). There are very few treatment options available for SCD, and even with optimal care SCD patients still suffer from a myriad of comorbidities to multiple organ systems and have a decreased life span. In this review, we will summarize results from trials of HSCT for children or adults with SCD using a variety of graft sources as well as conditioning and graft-versus-host disease prophylaxis regimen...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Transplantation for thalassemia major: alternative donors
Purpose of review: Lack of a human leukocyte antigen (HLA)-matched family donor is a major obstacle limiting the use of allogeneic hematopoietic stem cell transplantation (HSCT) to cure thalassemia major. Use of alternative donors, if found well tolerated enough, may be a viable option for transplantation in this setting, allowing to expand the number of patients treatable by HSCT. This review will provide an overview of alternative HSCT approaches in thalassemia major. Recent findings: With the introduction of high-resolution molecular HLA-typing techniques, the outcome of matched unrelated donor HSCT recipients has beco...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Matched sibling donor hematopoietic stem cell transplantation for thalassemia
Purpose of review: Bone marrow transplantation is the only curative treatment for severe thalassemia. Since its successful first report in 1981, more than 4000 patients with this disease worldwide underwent bone marrow transplantation. The purpose of this review is to update the most recent reports of matched sibling donor hematopoietic stem cell transplantation in thalassemia. Recent findings: Advanced and improved transplant techniques result in the improved outcomes in those transplants from a matched sibling donor with transplant-related mortality less than 5%. Class 3 patients aged at least 7 years and liver enlargem...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Allogeneic hematopoietic stem cell transplantation for dyskeratosis congenita
Purpose of review: Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure because of dyskeratosis congenita. The present review summarizes the literature with respect to the diagnosis and treatment of patients with dyskeratosis congenita who received HSCT, and discusses the recent progress in the management of dyskeratosis congenita. Recent findings: The recent systematic review of the literature showed poor long-term outcome, with 10-year survival estimates of only ...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Hematopoietic stem cell transplantation for acquired aplastic anemia
Purpose of review: There has been a steady improvement in outcomes with allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA), because of progress in optimization of the conditioning regimens, donor hematopoietic cell source, and supportive care. Here, we review recently published data that highlight the improvements and current issues in the treatment of SAA. Recent findings: Approximately one-third of aplastic anemia patients treated with immune suppressive therapy (IST) have acquired mutations in myeloid cancer candidate genes. Because of the greater probability for eventual failure of IST, huma...
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Allogeneic stem cell transplantation for nonmalignant diseases
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: ALLOGENEIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES: Edited by Andrea Bacigalupo Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 6, 2016 Category: Hematology Tags: Editorial Introduction Source Type: research

Molecular basis of inherited thrombocytopenias: an update
Purpose of review: Inherited thrombocytopenias are a heterogeneous group of diseases caused by mutations in many genes. They account for approximately only 50% of cases, suggesting that novel genes have yet to be identified for a comprehensive understanding of platelet biogenesis defects. This review provides an update of the last year of discoveries on inherited thrombocytopenias focusing on the molecular basis and potential pathogenic mechanisms affecting megakaryopoiesis and platelet production. Recent findings: Most of the novel discoveries are related to identification of mutations in novel inherited thrombocytopenia...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

Controversies in the treatment of immune thrombocytopenia
Purpose of review: We address three current controversies in management of immune thrombocytopenia (ITP): Should asymptomatic children with newly diagnosed ITP and severe thrombocytopenia be treated? Does intensification of up-front therapy in adults with newly diagnosed ITP impact long-term outcomes? Is splenectomy still the second-line treatment of choice in adults with chronic ITP? Recent findings: Severe bleeding is rare in children with ITP. There is little evidence that the platelet count predicts or that treatment prevents severe bleeding in this population. Intensified treatment with high-dose dexamethasone and ri...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

How much do we really know about von Willebrand disease?
Purpose of review: In the last nine decades, large advances have been made toward the characterization of the pathogenic basis and clinical management of von Willebrand disease (VWD), the most prevalent inherited bleeding disorder. Pathological variations at the von Willebrand factor (VWF) locus present as a range of both quantitative and qualitative abnormalities that make up the complex clinical spectrum of VWD. This review describes the current understanding of the pathobiological basis of VWD. Recent findings: The molecular basis of type 2 (qualitative abnormalities) and type 3 VWD (total quantitative deficiency) have...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

Management of heparin-induced thrombocytopenia
Purpose of review: The purpose of this review is to summarize recent findings on heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating IgG targeting platelet factor 4 (PF4)/polyanion complexes. Recent findings: HIT can explain unusual clinical events, including adrenal hemorrhages, arterial/intracardiac thrombosis, skin necrosis, anaphylactoid reactions, and disseminated intravascular coagulation. Sometimes, HIT begins/worsens after stopping heparin (‘delayed-onset’ HIT). Various HIT-mimicking disorders are recognized (e.g., acute disseminated intravascular coagulation/...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

The role of the tissue factor pathway in haemostasis and beyond
Purpose of review: The role of tissue factor (TF) in the initiation of the blood coagulation network leading to generation of a fibrin clot has been well defined over the past 50 years. Although much is known about this sequence of events and its regulation, many important questions remain unresolved. More recently, a complex role for TF in cellular processes independent of fibrin generation has emerged. This review summarizes some of the advances in this field. Recent findings: TF is the cellular receptor and cofactor for factor VII/VIIa; however, controversy still surrounds expression of TF within the vasculature, the r...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

Antithrombotic potential of the contact activation pathway
This report examines the mechanism(s) by which each protein of the contact activation system – factor XII (FXII), high-molecular-weight kininogen, and prekallikrein – influences thrombosis risk. Recent findings: FXII generates thrombin through contact activation via interaction with artificial surfaces as on medical instruments such as indwelling catheters, mechanical valves, stents, and ventricular assist devices. Inhibition of FXIIa-mediated contact activation prevents thrombosis under contact activation circumstances without affecting hemostasis. Current studies suggest that high-molecular-weight kininogen ...
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Robert I. Handin Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 5, 2016 Category: Hematology Tags: Editorial Introduction Source Type: research

The curious origins of angioimmunoblastic T-cell lymphoma
Purpose of review: Once an obscure disease, recent studies have transformed our understanding of angioimmunoblastic T-cell lymphoma (AITL). In this review, we summarize new major advances in the genetics and biology of AITL. Recent findings: Genome wide sequencing studies have dissected the repertoire of the genetic alterations driving AITL uncovering a highly recurrent Gly17Val somatic mutation in the small GTPase RHOA and major role for mutations in epigenetic regulators, such as TET2, DNMT3A and IDH2, and signaling factors (e.g., FYN and CD28). These findings support a multistep model of follicular T helper cell transf...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma
Purpose of review: Multiple myeloma is a plasma cell malignancy evolving in the bone marrow and leading to end organ damage such as bone lesions, cytopenias, and kidney failure. This review delineates recent advances in the molecular mechanisms leading to tumor progression in multiple myeloma. Two different aspects enable tumor expansion: cell autonomous through genomic alterations in the tumor clone and noncell autonomous deregulations in the bone marrow tumor microenvironment. These alterations provide the framework for the continuous progression of multiple myeloma from early precursor conditions such as monoclonal gamm...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Histiocytic neoplasms in the era of personalized genomic medicine
Purpose of review: Since the discovery of B-Raf proto-oncogene (BRAF) V600E mutations in histiocytic neoplasms, diverse kinase alterations have been uncovered in BRAF V600E-wildtype histiocytoses. The purpose of this review is to outline recent molecular advances in histiocytic neoplasms and discuss their impact on the pathogenesis and treatment of these disorders. Recent findings: Activating kinase alterations discovered in BRAF V600E-wildtype Langerhans (LCH) and non-Langerhans cell histiocytoses (non-LCH) result in constitutive activation of the mitogen-activated protein kinase and/or phosphoinositide 3-kinases-Akt mur...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Group 3 innate lymphoid cells in tissue damage and graft-versus-host disease pathogenesis
Purpose of review: Innate lymphoid cells (ILC) have emerged as modulators of conditioning-induced tissue damage and development of graft-versus-host disease (GVHD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). This review highlights experimental and clinical evidence for a role of ILC in GVHD pathogenesis. Recent findings: ILC are well known for their role in epithelial homeostasis and innate immunity. In addition, recent studies identified ILC as architects of intestinal responses to tissue damage after experimental radio and chemotherapy. Group 3 ILC, and their signature cytokine IL-22, ca...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Role of the CARMA1/BCL10/MALT1 complex in lymphoid malignancies
Purpose of review: The CARMA1/BCL10/MALT1 (CBM) complex is a multimeric signaling complex controlling several important aspects of lymphocyte activation. Gain-of-function mutations in the genes encoding CBM proteins or their upstream regulators are associated with lymphoid malignancies, whereas loss-of-function mutations lead to immunodeficiency. This review reports on recent findings advancing our understanding of how CBM proteins contribute to malignant and nonmalignant hematological diseases in humans. Recent findings: Somatic gain-of-function mutations of CARMA1 (also known as CARD11), originally described for patient...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Genetic and epigenetic determinants of B-cell lymphoma evolution
Purpose of review: The success of targeted therapies fostered the development of increasingly specific and effective therapeutics for B-cell malignancies. However, cancer plasticity facilitates disease relapse, whereby intratumoral heterogeneity fuels tumor evolution into a more aggressive and resistant form. Understanding cancer heterogeneity and the evolutionary processes underlying disease relapse is key for overcoming this limitation of current treatment strategies. In the present review, we delineate the current understanding of cancer evolution and the advances in both genetic and epigenetic fields, with a focus on n...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

The routes for transformation of follicular lymphoma
Purpose of review: Aggressive transformation, a frequent event in the natural history of follicular lymphoma, is associated with increased lymphoma-related mortality and yet the underlying biology remains poorly defined. This review outlines recent advances in our understanding of the genetic basis and evolutionary process leading to transformation. Recent findings: Both the antecedent indolent and transformed follicular lymphoma (tFL) arise through branched divergent evolution with tumors emerging from a founder precursor population, the common progenitor cell. Although the majority of tFLs maintain a germinal center B-c...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

The many layers of epigenetic dysfunction in B-cell lymphomas
Purpose of review: Perturbation of the epigenome is emerging as a central driving force in the pathogenesis of diffuse large B-cell lymphomas (DLBCL) and follicular lymphoma. The purpose of this review is to explain how alteration of different layers of the epigenome contributes to the biology and clinical features of these tumors. Recent findings: Key new findings implicate DNA methylation heterogeneity as a core feature of DLBCL. Epigenetic diversity is linked to unfavorable clinical outcomes, clonal selection at relapse, and is driven at least in part because of the actions of activation-induced cytosine deaminase, whi...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Chemotherapy-sparing treatment strategies for follicular lymphoma: current options and future directions
Purpose of review: The accelerating development of targeted therapy offers the possibility of avoiding the many toxic side-effects of cytotoxic chemotherapy often experienced during treatment of patients with malignancies. As a currently incurable disease that typically follows an indolent course, follicular lymphoma is a disease for which chemotherapy-free treatment may offer substantial benefit. Recent findings: We review chemotherapy-free treatment regimens, including those targeting cell-surface proteins and intracellular signaling pathways currently in use for the treatment of follicular lymphoma, paying particular a...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders
This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. Recent findings: NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell ma...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Deregulation of the HOXA9/MEIS1 axis in acute leukemia
Purpose of review: HOXA9 is a homeodomain transcription factor that plays an essential role in normal hematopoiesis and acute leukemia, in which its overexpression is strongly correlated with poor prognosis. The present review highlights recent advances in the understanding of genetic alterations leading to deregulation of HOXA9 and the downstream mechanisms of HOXA9-mediated transformation. Recent findings: A variety of genetic alterations including MLL translocations, NUP98-fusions, NPM1 mutations, CDX deregulation, and MOZ-fusions lead to high-level HOXA9 expression in acute leukemias. The mechanisms resulting in HOXA9...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Telomerase in hematologic malignancies
Purpose of review: The activation of telomere maintenance pathways has long been regarded as a key hallmark of cancer and this has propelled the development of novel inhibitors of telomerase. In this review, we detail the background biology on telomere maintenance in health and disease, then concentrate on the recent preclinical and clinical development behind targeting telomerase in blood cancers. Recent findings: Preclinical and clinical studies have shown that imetelstat, a competitive inhibitor of telomerase, has activity in certain hematologic malignancies, in particular the myeloproliferative neoplasms and acute mye...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Microenvironmental regulation of hematopoietic stem cells and its implications in leukemogenesis
Purpose of review: Hematopoietic stem cells (HSCs) are a population of cells in the bone marrow which can self-renew, differentiate into late lineage progenitors, or remain quiescent. HSCs exist alongside several cell types in the bone marrow microenvironment that comprise the stem cell niche. These cells regulate HSC function and can contribute to leukemogenesis. In this review we will discuss recent advances in this field. Recent findings: In the vascular niche, arteriolar and sinusoidal zones appear to play distinct roles in HSC function. Endothelial cells modulate HSC function via Notch and other signaling pathways. I...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Heterogeneity of the bone marrow niche
Purpose of review: The bone marrow niche is increasingly recognized as heterogeneous with specific subtypes of mesenchymal niche cells governing the development or homeostasis of selective parenchymal hematopoietic subsets. The present review outlines recent efforts in dissecting these microniches regulated by unique cell pairings within the bone marrow and provides an overview of how the bone marrow orchestrates multiple facets of hematopoiesis. Recent findings: Recent advancement in technologies has significantly improved our understanding of the cellular and molecular constituents that contribute to regulation of hemat...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Role of Tat-interacting protein of 110 kDa and microRNAs in the regulation of hematopoiesis
Purpose of review: Hematopoiesis is regulated by cellular factors including transcription factors, microRNAs, and epigenetic modifiers. Understanding how these factors regulate hematopoiesis is pivotal for manipulating them to achieve their desired potential. In this review, we will focus on HIV-1 Tat-interacting protein of 110 kDa (Tip110) and its regulation of hematopoiesis. Recent findings: There are several pathways in hematopoiesis that involve Tip110 regulation. Tip110 is expressed in human cord blood CD34+ cells; its expression decreases when CD34+ cells begin to differentiate. Tip110 is also expressed in mouse m...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

The mitochondrial metabolic checkpoint and aging of hematopoietic stem cells
Purpose of review: Cell-cycle checkpoints are surveillance mechanisms in eukaryotic cells that monitor the condition of the cell, repair cellular damages, and allow the cell to progress through the various phases of the cell cycle when conditions become favorable. We review recent advances in hematopoietic stem cell (HSC) biology, highlighting a mitochondrial metabolic checkpoint that is essential for HSCs to return to the quiescent state. Recent findings: As quiescent HSCs enter the cell cycle, mitochondrial biogenesis is induced, which is associated with increased mitochondrial protein folding stress and mitochondrial o...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Hematopoietic stem cell lineage specification
Purpose of review: Hematopoietic stem cells (HSCs) possess two fundamental characteristics, the capacity for self-renewal and the sustained production of all blood cell lineages. The fine balance between HSC expansion and lineage specification is dynamically regulated by the interplay between external and internal stimuli. This review introduces recent advances in the roles played by the stem cell niche, regulatory transcriptional networks, and metabolic pathways in governing HSC self-renewal, commitment, and lineage differentiation. We will further focus on discoveries made by studying hematopoiesis at single-cell resolut...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

‘Waterloo’: when normal blood cells meet leukemia
Purpose of review: Mortality and morbidity associated with leukemia are largely due to frequently occurring cytopenias or the dysfunction of normal blood cells in patients. Our knowledge of how normal blood cells degenerate in response to leukemic cell infiltration has been quite limited. This review summarizes recent findings and discusses both extrinsic and intrinsic mechanisms underlying the suppression of normal hematopoiesis in leukemia. Recent findings: Recent studies have shown that leukemic cells are able to remodel the bone marrow niche by secreting specific cytokines or dampening its hematopoietic-supporting fun...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different
Purpose of review: Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Recent findings: Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. ...
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - June 4, 2016 Category: Hematology Tags: Editorial Introductions Source Type: research

Regulation of VWF expression, and secretion in health and disease
Purpose of review: Von Willebrand factor (VWF) is a large multidomain, multimeric glycoprotein that plays an essential role in regulating the balance between blood clotting and bleeding. Aberrant VWF regulation can lead to a spectrum of diseases extending from bleeding disorders [Von Willebrand disease (VWD)] to aberrant thrombotic thrombocytopenic purpura (TTP). Understanding the biology of VWF expression and secretion is essential for developing novel targeted therapies for VWF-related hemostasis disorders. Recent findings: A number of recent elegant in-vitro and in-vivo studies will be highlighted, including the discov...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Extracellular matrix proteins in the regulation of thrombus formation
Purpose of review: Exposure of subendothelial extracellular matrix (ECM) proteins to the circulation is the key event that initiates platelet accumulation and clot formation after vessel injury. Soluble ECM proteins are also essential for support and regulation of these events. This review discusses the current understanding of ECM proteins in thrombosis and hemostasis. Recent findings: Fibrinogen and von Willebrand factor (VWF) are considered essential for thrombosis and hemostasis. Interestingly, αIIbβ3 integrin-dependent thrombus formation persists in the absence of fibrinogen and VWF, suggesting that other ...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Integration of endothelial protease-activated receptor-1 inflammatory signaling by ubiquitin
Purpose of review: The maintenance and integrity of the endothelial barrier is essential for vascular homeostasis. Endothelial barrier dysfunction is mediated by various inflammatory factors, many of which act through G protein-coupled receptors including protease-activated receptors (PARs). PARs are expressed in multiple cell types in the vasculature and mediate cellular responses to thrombin, the key effector protease of the coagulation cascade. Thrombin activation of PAR1 induces endothelial barrier permeability through multiple pathways. Here, we discuss the mechanism by which thrombin activation of PAR1 promotes endot...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia
Purpose of review: To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions. Recent findings: Cross-talk between bone marrow tumor cells and surrounding cells, including endothelial cells, is important for tumor growth in hematologic neoplasia. In addition to conventional signaling pathways, exosomes, which are small endosome-derived vesicles containing miRNAs, can help to modulate the microenvironment without directly contacting nontumorous cells....
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature
Purpose of review: Long recognized for its role in regulation of vascular endothelial growth factor signaling, neuropilin (Nrp)1 has emerged as a modulator of additional signaling pathways critical for vascular development and function. Here we review two novel functions of Nrp1 in blood vessels: regulation of transforming growth factor-β (TGFβ) signaling in endothelial cells and regulation of platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells. Recent findings: Novel mouse models demonstrate that Nrp1 fulfills vascular functions independent of vascular endothelial growth factor signa...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31)
Purpose of review: The purpose of this article is to describe the function of the vascular cell adhesion and signaling molecule, platelet/endothelial cell adhesion molecule-1 (PECAM-1), in endothelial cells, with special emphasis on its role in maintaining and restoring the vascular permeability barrier following disruption of the endothelial cell junction. Recent findings: In addition to its role as an inhibitory receptor in circulating platelets and leukocytes, PECAM-1 is highly expressed at endothelial cell–cell junctions, where it functions as an adhesive stress-response protein to both maintain endothelial cell...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Membrane-anchored proteases in endothelial cell biology
Purpose of review: The endothelial cell plasma membrane is a metabolically active, dynamic, and fluid microenvironment where pericellular proteolysis plays a critical role. Membrane-anchored proteases may be expressed by endothelial cells as well as mural cells and leukocytes with distribution both inside and outside of the vascular system. Here, we will review the recent advances in our understanding of the direct and indirect roles of membrane-anchored proteases in vascular biology and the possible conservation of their extravascular functions in endothelial cell biology. Recent findings: Membrane-anchored proteases bel...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Pulling on my heartstrings: mechanotransduction in cardiac development and function
Purpose of review: Endothelial cells line the surface of the cardiovascular system and display a large degree of heterogeneity due to developmental origin and location. Despite this heterogeneity, all endothelial cells are exposed to wall shear stress (WSS) imparted by the frictional force of flowing blood, which plays an important role in determining the endothelial cell phenotype. Although the effects of WSS have been greatly studied in vascular endothelial cells, less is known about the role of WSS in regulating cardiac function and cardiac endothelial cells. Recent findings: Recent advances in genetic and imaging tech...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

The why's and wherefore's of this vascular biology section of Current Opinion in Hematology
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

New insights into sickle cell disease: mechanisms and investigational therapies
Purpose of review: Sickle cell disease (SCD) afflicts millions worldwide. The simplicity of its single nucleotide mutation belies the biological and psychosocial complexity of the disease. Despite only a single approved drug specifically for the treatment of SCD, new findings reviewed from 2015 provide the direction forward. Recent findings: The last year has provided a wealth of support for mechanisms affecting the red cell, hemolysis and vasculopathy, the innate immune system activation, blood cell and endothelial adhesiveness, central sensitization to pain, and chronic brain injury. The evidence supporting expanded use...
Source: Current Opinion in Hematology - April 9, 2016 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Mohandas Narla Source Type: research